BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS Original Article PANKAJ KUMAR JAISWAL, SANJOY DAS, MALAY K. DAS Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004, India * * Received: 31 Dec 2020, Revised and Accepted: 09 Mar 2021 Email: mkdps@dibru.ac.in ABSTRACT Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis. Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin- loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)- induced psoriasis rat model. Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm 2 Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis. /h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels. Keywords: Lipid-polymer hybrid nanoparticles, Curcumin, Topical gels, Psoriasis, Imiquimod © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021v13i3.40668. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Psoriasis is a consistently recurring, autoimmune, chronic inflammatory disorder of the skin that is estimated to affect approximately 2-4% of the population in Western countries and shows lower prevalence in Asian as well as African countries [1, 2]. The main pathological features of psoriasis are multifactorial, usually involving hyperplasia of the epidermis, abnormal genetic association and dysregulated signal processing of T cells as well as an imbalance between inflammatory mediators that promote the infiltration of leukocytes [3, 4]. Though major problems associated with psoriasis are relapsing and spontaneous remission, which may trigger by genetic, environmental and several other factors [5]. As there is no complete resolution for psoriasis to date, a stepwise strategy to healing is often employed with the initial use of topical treatment, act to phototherapy and pharmacotherapy. However, the presence of multilayered epidermal barriers of psoriatic skin causes hindrance to the entry of drug molecules to the inflamed site, resulting in the formation of severe adverse effects [6, 7]. To get better therapeutic benefits, several nanoparticles have been widely explored for topical drug delivery, including polymeric, lipid, metallic, carbon-based and vesicular nanoparticles. These nanoparticles are shown to be promising in dermatological disease management by boosting drug solubility and bioavailability of poorly water-soluble drugs [8-13]. Nevertheless, single nanoparticles unable to provide these benefits at a time and have some common limitations in terms of rapid drug diffusion, instability during storage and uncontrolled drug release [14-16]. Recently, lipid-polymer hybrid nanoparticles (LPHNPs) have gained much attention as their outstanding benefits to resolve these problems. This system can take the functions of the lipid and polymeric nanoparticles, which comprises two distinct components i.e., an innermost hydrophobic polymeric core which encapsulating the poorly water-soluble drugs and an outermost lipid layer that act as a molecular fence to promote drug retention inside the polymeric core. Although for topical application, these hybrid nanoparticles have been incorporated into hydrogels, which makes the formulation very pertinent to achieving the desired effect [17, 18]. Curcumin is a yellow-colored polyphenolic compound obtained from the rhizome of the perennial herb Curcuma longa and possesses outstanding anticancer properties [19]. Despite the promising therapeutic value offered by curcumin, its translation from basic research to clinical application is limited due to poor water solubility and low bioavailability [20, 21]. Therefore, the present study was engineered to develop and characterize the LPHNP based hydrogels for the topical delivery of curcumin and compares the in vivo anti-psoriatic efficacy with the commercial marketed product in hopes of assessing a relatively effective and safe medicine for the psoriasis treatment. MATERIALS AND METHODS Materials Curcumin and stearic acid were purchased from Hi-Media Laboratories Pvt. Ltd., Mumbai, India. Ethylcellulose was purchased from Loba Chemie Pvt. Ltd., Mumbai, India. Polyethylene glycol 400 and tween 80 were purchased from Sisco Research Laboratories Pvt. Ltd., Mumbai, India. Carbopol 934, ethanol and triethanolamine were purchased from Research Lab Fine Chem Industries, Mumbai, India. All other reagents and chemicals used were of analytical grade. Preparation of lipid-polymer hybrid nanoparticles (LPHNPs) The LPHNPs were prepared by the emulsification solvent evaporation method with slight modifications [22, 23]. Briefly, stearic acid and ethyl cellulose were dissolved in 2 ml of ethanol in a beaker and curcumin was added into the lipid-polymer (oil) phase. Resulting lipid-polymer (oil) phase was added dropwise into 10 ml of aqueous phase (1% w/v Tween 80) under continuous stirring at 15000 rpm for 5 min using a homogenizer (Ultra-Turrax T 25 International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Issue 3, 2021